1. Field of the Invention
The present invention relates to biodegradable guide channels, processes for their preparation, and methods for their use in various surgical applications, specifically in the microsurgery of anatomical sites where conditions of discontinuity and/or loss of substance have occurred.
2. Description of Related Art
Research to identify alternative surgical techniques to treat, in particular, lesions to the peripheral nerves and various parts of the anatomy where conditions of discontinuity and/or loss of substance have occurred, such as in tendon surgery, has been described in the literature. Most of the studies performed so far have specifically focused on the treatment of trauma to the peripheral nerves, as described in more detail infra. However, special attention is now being paid to tendon surgery, for which the use of gelatin tubes, cellophane, or polyethylene structures, which give rise to rejection phenomena, have already been described. More recently, materials composed of regenerated, oxidized cellulose have been studied (Meislin R. J. et al., J. of Applied Biomaterials 1, 13-19, 1990).
A considerable part of such research has, however, been focused on the use of guide channels or tubular replacements for use as supports in the regeneration of damaged nerves in the treatment of trauma to the peripheral nerves.
These tubular replacements allow the two severed nerve ends to be held in proximity to each other, thus enabling the nerve to regenerate under suitable biological conditions. Moreover, these tubes inhibited or delayed the effects of infiltration linked with the connective tissue. Some guide channels or replacements made for these purposes with various polymers or their derivatives are already known (Ducker at al., Vol. 28, J. Neurosurg., 582-587, 1968; Midgley et al., Vol. 19, Surgical Forum, 519-528, 1968; Lundborg et al., Vol. 41, J. Neuropath. in Exp. Neurol., 412-422, 1982; Molander at al., Vol. 5, Muscle & Nerve, 54-58, 1982; Uzman at al., Vol. 9, J. Neurosci. Res. 325-338, 1983; Nyilas at al., Vol. 29, Transactions Am. Soc. Artif. Internal Organs, 307-313, 1983; and U.S. Pat. No. 4,534,349, 1985).
In order to increase functional recovery of the damaged nerve, tubular replacements have been prepared with biological polymers and mixtures of the same traditionally used in nerve repair (Madison et al., Vol. 44, Brain Res., 325-334, 1985; Yannas et al., Vol. 11, Trans. soc. Biomat. 146, 1985; Williams et al., Vol. 264, J. Comp. Neurol. 284-290, 1987). The possibility of including various growth factors in these tubular replacements has been studied (Politis at al., Vol. 253, Brain Res. 1-12, 1982; Aebischer at al., PCT WO 90/05552). The drawbacks of including growth factors in these tubular replacements by known methods is due to the fact that they are not stable in aqueous solutions, their half-lives are measured in hours rather than in weeks, the latter being the time necessary for complete nerve regeneration. Under these conditions, the release of these factors cannot be controlled, and they are often administered in the form of a bolus, which does not allow sufficiently long-lasting stimulation of the nerve cells required for regeneration.
A further step forward in the area of tubular replacements is represented by the preparation of polymers with which it is possible to make biocompatible and biodegradable replacements which remain in place according to the degree of chemical modification of the natural polymer and on the type of substitute used (Favaro G. et al., XXXVI Trans. Am. Soc. Artif. Organs, M291-M294, 1990). In this case too, the two nerve stumps are fixed within the tubular channel by sutures. Moreover, these materials have the added advantage of providing a guide for nerve regeneration, with the possibility of allowing the new growth to occur in the proper environment once the material used has been absorbed.
Various methods have been proposed for the preparation of guide channels with biocompatible and bioabsorbable materials. The most simple and rapid technique is the extrusion of a solution of biocompatible and bioabsorbable material through suitable holes.
Limitations on the use of guide channels made with some biocompatible and bioabsorbable materials, produced by extrusion or other manufacturing techniques, is their more or less marked tendency to tear when the nerve stumps are stitched to them.
There therefore exists a need for biocompatible and bioabsorbable guide channels with particular physicochemical and biological characteristics, particularly for those guide channels which contain specific trophic factors and/or compounds with bioactivity for a specific anatomical target, which permit then to be used to great advantage in surgery and microsurgery of the peripheral nerves or other anatomical areas in which conditions of discontinuity and/or loss of substance occur, and in which it is necessary to prevent the incidence and recurrence of post-operative adherences.